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Abstract Tension-adhesion interplay is a crucial mechanism in multicellular organisms that determines the tension differential among internal and external interfaces, which in turn, mediates tissue surface tension and cell sorting, morphogenesis and remodeling, and cancer progression. Cadherins are widely believed to be involved, yet key aspects of the process are neither well characterized nor quantified. This study demonstrates the critical role of N-cadherin in driving tension polarization throughout the actin cortical network. N-cadherin regulates both tension increase at the cell-medium (external) interface and decrease at the cell-cell (internal) interface, and their quantitative magnitudes, both absolute and relative, strongly depend on the surface density of N-cadherin. Furthermore, the strength of tension polarization also increases with respect to the number of cell-cell interfaces for cells within a multicellular cluster. The cadherin-actin contractility linkage is mediated by Rac1, which serves as a molecular switch to trigger cortex remodeling and contraction via myosin II. Inhibition of Rac1 activity decreases tension polarization and leads to reduced coherence in both small clusters and spheroids. These results provide a pathway to reconcile opposing theories for tissue surface tension generation and perspectives in cancer treatment.

Purpose: This study aims to investigate the association between blood estradiol level and two different etiologies of corneal ectasia in premenopausal women., Methods: This is an observational case-control study with three groups of women. Group 1 included women with keratoconus. Group 2 included women with post refractive surgery ectasia (PRSE). Group 3 was the control group. Venous blood for the measurement of estradiol was collected in order to assess the relationship between estradiol levels and ectasia. Participant's age, regular cycle (yes/no) and oral contraceptive pills (OCP) use (yes/no) was also documented. We compared the differences in estradiol levels between the 3 groups. Logistic regression was used to detect variables' effect on participants' chance to ectasia., Results: Ninety-six women were enrolled: 36 (37%), 29 (30%), and 31 (32%) in the keratoconus, PRSE, and control group, respectively. The mean age of the participants was 29.8 ± 3.2, 31.9 ± 2.6, and 30.7 ± 3.5 years, respectively (p = 0.04, between groups 1 and 2). Estradiol levels [pg/mL] were 38.0 ± 2.4, 43.4 ± 2.4, and 28.6 ± 3.9, respectively ( p  < 0.001, between any pair of groups). Two multivariate logistic regression models adjusted to age, regular cycle, and OCP use, indicated that higher blood estradiol levels were associated with an increased risk of ectasia (OR = 2.71 and 2.44, respectively; p  < 0.001)., Conclusion: Corneal ectasia may be associated with elevated blood estradiol levels. Estradiol measurements could be useful in women with keratoconus or in women who undergo refractive surgery., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Objectives: Gut microbial symbionts have been shown to influence the development of autoimmunity in multiple sclerosis (MS). Emerging research points to an important relationship between the microbial-IgA interface and MS pathophysiology. IgA-secreting B cells are observed in the MS brain, and shifts in gut bacteria-IgA binding have been described in some patients with MS. However, the relationships between the gut microbiome and the host immune response, particularly regarding B-cell-depleting immunomodulation, remain underexplored. This study aimed to evaluate the composition of the gut microbiome in patients with newly diagnosed MS at baseline and after B-cell depletion, using long-read sequencing for enhanced taxonomic resolution. We further aimed to investigate the host/microbiome interface by evaluating microbe/immunoglobulin A relationships., Methods: We collected stool samples from 43 patients with newly diagnosed, untreated MS and 42 matched healthy controls. Nineteen patients with MS initiated anti-CD20 monoclonal antibody treatment and donated additional stool samples after 6 months of treatment. We evaluated the host-microbial interface using bacterial flow cytometry and long-read 16S rRNA gene amplicon sequencing. We used Immune Coating Scores to compare the proportions of bacteria identified in the IgA-coated vs IgA-uncoated bacterial fractions., Results: Patients with untreated, newly diagnosed MS showed significant reductions in IgA-bound fecal microbiota compared with controls. Using multiple linear regression models adjusted for potential confounders, we observed significant ( p < 0.05) changes in the abundance and prevalence of various strain-level gut bacteria amplicon sequence variants (ASVs) within both total and IgA-coated bacterial fractions. Some changes (e.g., decreased relative abundance of a Faecalibacterium prausnitzii variant in MS) were consistent with previous reports, while others (e.g., increased relative abundance and prevalence of Monoglobus pectinyliticus in MS) were novel. Immune Coating Scores identified subsets of organisms for which normal IgA-coating patterns were disrupted at the onset of MS, as well as those (particularly Akkermansia muciniphila ) whose IgA-coating became more aligned with controls after therapy., Discussion: This analysis of gut microbial ASVs reveals shifts in taxonomic strains induced by immune modulation in MS.

To perform most behaviors, animals must send commands from higher-order processing centers in the brain to premotor circuits that reside in ganglia distinct from the brain, such as the mammalian spinal cord or insect ventral nerve cord. How these circuits are functionally organized to generate the great diversity of animal behavior remains unclear. An important first step in unraveling the organization of premotor circuits is to identify their constituent cell types and create tools to monitor and manipulate these with high specificity to assess their function. This is possible in the tractable ventral nerve cord of the fly. To generate such a toolkit, we used a combinatorial genetic technique (split-GAL4) to create 195 sparse driver lines targeting 196 individual cell types in the ventral nerve cord. These included wing and haltere motoneurons, modulatory neurons, and interneurons. Using a combination of behavioral, developmental, and anatomical analyses, we systematically characterized the cell types targeted in our collection. In addition, we identified correspondences between the cells in this collection and a recent connectomic data set of the ventral nerve cord. Taken together, the resources and results presented here form a powerful toolkit for future investigations of neural circuits and connectivity of premotor circuits while linking them to behavioral outputs.

Cardiac T1 mapping is a valuable quantitative MRI technique for diagnosing diffuse myocardial diseases. Traditional methods, relying on breath-hold sequences and cardiac triggering based on an ECG signal, face challenges with patient compliance, limiting their effectiveness. Image registration can enable motion-robust cardiac T1 mapping, but inherent intensity differences between time points pose a challenge. We present MBSS-T1, a subject-specific self-supervised model for motion correction in cardiac T1 mapping. Physical constraints, implemented through a loss function comparing synthesized and motion-corrected images, enforce signal decay behavior, while anatomical constraints, applied via a Dice loss, ensure realistic deformations. The unique combination of these constraints results in motion-robust cardiac T1 mapping along the longitudinal relaxation axis. In a 5-fold experiment on a public dataset of 210 patients (STONE sequence) and an internal dataset of 19 patients (MOLLI sequence), MBSS-T1 outperformed baseline deep-learning registration methods. It achieved superior model fitting quality (R 2 : 0.975 vs. 0.941, 0.946 for STONE; 0.987 vs. 0.982, 0.965 for MOLLI free-breathing; 0.994 vs. 0.993, 0.991 for MOLLI breath-hold), anatomical alignment (Dice: 0.89 vs. 0.84, 0.88 for STONE; 0.963 vs. 0.919, 0.851 for MOLLI free-breathing; 0.954 vs. 0.924, 0.871 for MOLLI breath-hold), and visual quality (4.33 vs. 3.38, 3.66 for STONE; 4.1 vs. 3.5, 3.28 for MOLLI free-breathing; 3.79 vs. 3.15, 2.84 for MOLLI breath-hold). MBSS-T1 enables motion-robust T1 mapping for broader patient populations, overcoming challenges such as suboptimal compliance, and facilitates free-breathing cardiac T1 mapping without requiring large annotated datasets. Our code is available at https://github.com/TechnionComputationalMRILab/MBSS-T1., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Objective: Intracranial pressure monitoring (ICPM) is a cornerstone procedure in the management of severe traumatic brain injury (TBI). Yet, its implementation is low and the impact on outcomes debated. The authors' objective was to determine the association between ICPM and 1-year mortality in severe TBI., Methods: The authors performed a retrospective cohort study utilizing data from the Israel National Trauma Registry (INTR) of severe TBI patients admitted to level I trauma centers from 2015 to 2021. Multivariable logistic regressions were performed to calculate the odds ratio (OR) of 1-year mortality, adjusted for age, Glasgow Coma Scale (GCS) score, other severe injuries (nonhead Abbreviated Injury Scale [AIS] score ≥ 4), hypotension, and surgical decompression. The main outcome was 1-year mortality., Results: Of 2202 patients, 36.8% underwent insertion of ICPM. ICPM patients had a lower 1-year mortality rate (28.12% vs 33.60%, p = 0.015). Compared with ICPM, the adjusted odds of 1-year mortality of no ICPM were increased 1.2-fold (OR 1.21, 95% CI 0.96-1.54). The effect size was greater among patients with head AIS score 5-6 and age 18-64 years (OR 1.57, 95% CI 1.13-2.20) and age ≥ 65 years (OR 1.92, 95% CI 1.04-3.55); the effect size of no ICPM in those with head AIS score 3-4 was decreased (OR 0.49, 95% CI 0.26-0.93)., Conclusions: A significant association between ICPM and lower 1-year mortality in the most severe TBI patients (head AIS score 5-6) who were ≥ 18 years of age was observed. The authors' study supports the use of ICPM in severe TBI. The authors recommend more detailed reporting to best inform quality improvement programs on a national scale. This research contributes to the academic dialogue on TBI and the considerations for enhancing patient care.

Recently, we proposed a universal scaling framework that shows shear thickening in dense suspensions is governed by the crossover between two critical points: one associated with frictionless isotropic jamming and a second corresponding to frictional shear jamming. Here, we show that orthogonal perturbations to the flows, an effective method for tuning shear thickening, can also be folded into this universal scaling framework. Specifically we show that the effect of adding orthogonal shear perturbations can be incorporated into the scaling variable via a multiplicative function, determined through our measurements, to achieve collapse of the entire thickening and dethickening dataset onto a single universal curve. We then show that this universal scaling framework can be used to control the phase behavior in thickening and jamming suspensions.

In 2014, the International Myeloma Working Group (IMWG) updated the criteria for diagnosing myeloma and added three additional criteria to the traditional Calcium elevation, Renal impairment, Anemia, Bone disease (CRAB) criteria, called the Sixty % marrow plama cells, Light chain ratio >60, Mri demonstates lytic lesions (SLiM) criteria (clonal bone marrow plasma cells ≥60%, involved to uninvolved free light chain ratio (FLCr) ≥100 and >1 focal lesion on magnetic resonance imaging (MRI)). We report on the outcomes of 30 patients who underwent autologous stem cell transplantation (ASCT) where therapy was initiated solely based on SLiM criteria and compared them to a matched cohort of 60 patients whose myeloma-defining event was CRAB. The SLiM cohort had a shorter median time to neutrophil (15 vs. 16 days, p = 0.049) and platelet (15 vs. 17 days, p = 0.0004) engraftment. The 36-month overall survival (OS) was 100% in the SLiM group and 93.27% in the control group (95% CI 83.06%-97.42%), with a trend towards longer OS in the SLiM cohort (p = 0.065). The 36-month progression-free survival (PFS) was 91.61% in the SLiM (95% CI 69.93%-97.87%) and 65.95% in the control group (95% CI 52.31%-76.53%). There was no difference in the PFS between the cohorts (p = 0.414). ASCT is efficacious and safe in MM patients transplanted only due to SLIM criteria. Early intervention in this asymptomatic cohort did not appear to result in deeper responses or better PFS compared to outcomes in symptomatic patients., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Objective: To investigate the potential link between differences in bladder neck position and the occurrence of incidental asymptomatic urinary bladder gas on computed tomography (CT) scans in female patients., Methods: CT scans reports from January 2012 to December 2023 were analyzed in this retrospective study to identify adults presenting with bladder gas. Exclusion was based on factors such as prior urological procedures, urinary tract infections (UTIs), and other potential contributors to bladder gas. The distance between the bladder neck and the pubococcygeal line (B-PCL) was measured to assess bladder neck position. Patients without bladder gas, matched by age and sex, were selected as the control group. The B-PCL distances between the study and control groups were compared, and the reliability of the measurements was assessed through inter- and intra-reader agreement analysis., Results: Out of 1322 initial patients, 66 satisfied the inclusion criteria, with a median age of 70.9 years (IQR: 64.3-78.0) and a female majority (93.9 %). Among female patients, the median B-PCL distance was significantly shorter in the study group (5.3 mm) compared to controls (9.3 mm) (p = 0.002), suggesting a correlation between bladder neck position and bladder gas. Reliability measures indicated strong agreement among assessments (ICC > 0.95)., Conclusion: Preliminary findings suggest a correlation between lower bladder neck position and the presence of bladder gas on CT scans., Critical Relevance: This study sheds light on a possible association between bladder neck position and incidental bladder gas on CT scans, which may inform future diagnostic and clinical considerations., Key Points: Study examines bladder gas's incidental detection and bladder neck position via CT. Among females, shorter bladder neck to pubococcygeal line distance correlates with bladder gas. Identifying this link may suggest that a low bladder position could facilitate the presence of bladder gas., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Deep learning has revolutionized speech enhancement, enabling impressive high-quality noise reduction and dereverberation. However, state-of-the-art methods often demand substantial computational resources, hindering their deployment on edge devices and in real-time applications. Computationally efficient approaches like deep filtering and Deep Filter Net offer an attractive alternative by predicting linear filters instead of directly estimating the clean speech. While Deep Filter Net excels in noise reduction, its dereverberation performance remains limited. In this paper, we present a generalized framework for computationally efficient speech enhancement and, based on this framework, identify an inherent constraint within Deep Filter Net that hinders its dereverberation capabilities. We propose an extension to the Deep Filter Net framework designed to overcome this limitation, demonstrating significant improvements in dereverberation performance while maintaining competitive noise-reduction quality. Our experimental results highlight the potential of this enhanced framework for real-time speech enhancement on resource-constrained devices.

Background: Existing risk scores assessing geriatric vulnerability in the emergency department (ED) have shown limited predictive power, especially in diverse populations. We investigated the relationship of a quick and easy-to-administer geriatric vulnerability scoring system with functional decline and mortality in older patients admitted to multiple hospitals through the ED in the United States (US) and Brazil (BR)., Method: Federated, international, multicenter observational study of hospitalized ED patients aged ≥ 65 from US and BR. The six criteria from the PRO-AGE score (Physical impairment, Recent hospitalization, Older age [≥ 90], Acute mental alteration, Getting thinner, and Exhaustion; 0-8; higher scores = greater vulnerability) were assessed on admission. We used proportional hazards models to investigate the relationships between PRO-AGE score groups and 90-day mortality and functional decline, defined as new dependence in activities of daily living (ADL) and instrumental ADL (IADL), after adjusting for age, sex, race and ethnicity, education, Charlson comorbidity score, and study site. Death was considered a competing event for the functional decline outcome., Results: A total of 1390 patients were included (US = 560; Brazil = 830). The 90-day risk of death was higher for the upper compared with the lower (reference) PRO-AGE group in both cohorts (US: HR = 11.76; 95% confidence interval [CI] = 2.56-54.04; BR: HR = 12.29; 95% CI = 3.54-42.59), whereas the risk of new 90-day ADL disability was higher for upper (HR = 2.08; 95% CI = 1.21-3.56) and middle groups (HR = 2.10; 95% CI = 1.35-3.27) in the US but only the upper group in BR (HR = 1.70; 95% CI = 1.02-2.85)., Conclusion: A higher PRO-AGE score was associated with mortality and functional decline in older ED patients admitted to hospitals in the US and BR, demonstrating its generalizability as a geriatric vulnerability risk score., (© 2025 The American Geriatrics Society.)

Objectives: This study aims to conduct a gap analysis to determine the feasibility of mapping electronic health record data from the Clinical Emergency Data Registry (CEDR) to the Observational Medical Outcomes Partnership Common Data Model (OMOP-CDM)., Methods: We employed a structured approach using a custom-built comparison matrix. This matrix facilitated the alignment of CEDR data fields with the corresponding elements in the OMOP-CDM schema. Each field was evaluated for compatibility, with categorization into 3 distinct types: direct matches, fields requiring transformation, and fields with no OMOP-CDM equivalent. The mapping process was informed by consultations with the Observational Health Data Sciences and Informatics community forums and was guided by existing documentation and best practices in data harmonization. We performed descriptive analyses, quantifying the extent of direct matches and identifying the specific transformations needed for each CEDR-CDM field to ensure compliance with the OMOP-CDM model., Results: Our analysis indicates a high degree of compatibility between CEDR and OMOP, with over 90% (244/269) of CEDR fields being successfully mapped. Specifically, 173 fields had direct matches, whereas 71 required transformations. Challenges identified include addressing fields unique to CEDR with no OMOP-CDM equivalent and managing the transformations required for proper alignment., Conclusion: The OMOP-CDM presents a promising framework for standardizing emergency medicine data, thereby enhancing future query automation, analytics, and cross-institutional collaboration. Despite the potential challenges in capturing unique CEDR fields and addressing necessary transformations, most emergency department data can be standardized within the OMOP-CDM, fostering broader insights and applications in research and public health., Competing Interests: RAT receives grant funding from Beckman Coulter for unrelated work pertaining to artificial intelligence development around emergency department triage. The authors otherwise declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. PG, DS, AKV, KH, and SW also report receiving support from the Elevance Foundation for Opioid Response Efforts to support a national ED-based quality improvement network directed at opioid use disorder., (© 2024 The Author(s).)

Shape morphing is vital to locomotion in microscopic organisms but has been challenging to achieve in sub-millimetre robots. By overcoming obstacles associated with miniaturization, we demonstrate microscopic electronically configurable morphing metasheet robots. These metabots expand locally using a kirigami structure spanning five decades in length, from 10 nm electrochemically actuated hinges to 100 μm splaying panels making up the ~1 mm robot. The panels are organized into unit cells that can expand and contract by 40% within 100 ms. These units are tiled to create metasheets with over 200 hinges and independent electronically actuating regions that enable the robot to switch between multiple target geometries with distinct curvature distributions. By electronically actuating independent regions with prescribed phase delays, we generate locomotory gaits. These results advance a metamaterial paradigm for microscopic, continuum, compliant, programmable robots and pave the way to a broad spectrum of applications, including reconfigurable micromachines, tunable optical metasurfaces and miniaturized biomedical devices., Competing Interests: Competing interests: Q.L., P.L.M. and I.C. are inventors on a patent application (PCT/US2021/021419) submitted by Cornell University that covers electrically programmable microscale shape-memory actuators and related robotic devices. W.W., Q.L., M.F.R., P.L.M. and I.C. are inventors on a provisional patent application (63/267,190) submitted by Cornell University that covers actuators and control electronics for cilium metasurfaces and a provisional patent application (63/368,751) submitted by Cornell University that covers integrated circuits for controlling microscopic robots. The other authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Articular joints facilitate motion and transfer loads to underlying bone through a combination of cartilage tissue and synovial fluid, which together generate a low-friction contact surface. Traumatic injury delivered to cartilage and the surrounding joint capsule causes secretion of proinflammatory cytokines by chondrocytes and the synovium, triggering cartilage matrix breakdown and impairing the ability of synovial fluid to lubricate the joint. Once these inflammatory processes become chronic, posttraumatic osteoarthritis (PTOA) development begins. However, the exact mechanism by which negative alterations to synovial fluid leads to PTOA pathogenesis is not fully understood. We hypothesize that removing the lubricating macromolecules from synovial fluid alters the relationship between mechanical loads and subsequent chondrocyte behavior in injured cartilage. To test this hypothesis, we utilized an ex vivo model of PTOA that involves subjecting cartilage explants to a single rapid impact followed by continuous articulation within a lubricating bath of either healthy synovial fluid, phosphate-buffered saline (PBS), synovial fluid treated with hyaluronidase, or synovial fluid treated with trypsin. These treatments degrade the main macromolecules attributed with providing synovial fluid with its lubricating properties; hyaluronic acid and lubricin. Explants were then bisected and fluorescently stained to assess global and depth-dependent cell death, caspase activity, and mitochondrial depolarization. Explants were tested via confocal elastography to determine the local shear strain profile generated in each lubricant. These results show that degrading hyaluronic acid or lubricin in synovial fluid significantly increases middle zone chondrocyte damage and shear strain loading magnitudes, while also altering chondrocyte sensitivity to loading., (© 2024 Orthopaedic Research Society.)

The protein homeostasis (proteostasis) network encompasses a myriad of mechanisms that maintain the integrity of the proteome by controlling various biological functions, including protein folding and degradation. Alas, ageing-associated decline in the efficiency of this network enables protein aggregation and consequently the development of late-onset neurodegenerative disorders, such as Alzheimer's disease. Accordingly, the maintenance of proteostasis through late stages of life bears the promise to delay the emergence of these devastating diseases. Yet the identification of proteostasis regulators is needed to assess the feasibility of this approach. Here we report that knocking down the activity of the nucleolar FIB-1-NOL-56 complex protects model nematodes from proteotoxicity of the Alzheimer's disease-causing amyloid-β peptide and of abnormally long poly-glutamine stretches. This mechanism promotes proteostasis across tissues by modulating the activity of TGFβ signalling and by enhancing proteasome activity. Our findings point at research avenues towards the development of proteostasis-promoting therapies for neurodegenerative maladies., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)